Abstract

Background: Neurobiologic studies have suggested that dysregulation of central noradrenergic systems may be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD), and it has been hypothesized that genetic changes in the norepinephrine pathways might contribute to dysfunction of the prefrontal cortex circuits in ADHD. We previously reported decreased cerebral blood flow in the right lateral prefrontal cortex and both orbitofrontal cortices in children with ADHD. Genetic investigations have shown that the α-2A-adrenergic receptor gene (ADRA2A) is associated with ADHD. Our aim was to examine whether the presence of a risk allele of the ADRA2A MspI polymorphism is associated with differences in regional cerebral blood flow in boys with ADHD.

Results: We found regional hypoperfusion in the prefrontal regions, including the right orbitofrontal and right medial gyri, and the bilateral putamen and cerebellum in boys with ADHD relative to controls (p < 0.0005, uncorrected for multiple comparisons). Boys with ADHD who carried the C allele (n = 13) at the ADRA2AMspI polymorphism had reduced perfusion in the bilateral orbitofrontal regions compared with those without the C allele (n = 8) (p < 0.0005, uncorrected for multiple comparisons).

Limitations: This study was limited by the small sample size, and we did not obtain genetic data from the controls.

Conclusions: Our findings suggest that regional differences in cerebral perfusion in the orbitofrontal cortex represent an intermediate neuroimaging phenotype associated with the ADRA2AMspI polymorphism; these data support the validity of the noradrenergic hypothesis regarding the pathophysiology of ADHD.

Acknowledgments: This work was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF-2006–003-E00192).

Competing interests: None declared

Contributors: Drs. B.-N. Kim and J.-W. Kim contributed to the study’s conception and design. They, along with Drs. Cho, Shin and Yoo acquired the data. Drs. B.-N. Kim, J.-W. Kim, Kang, Hong and Lee analyzed the data. Drs. B.-N. Kim, J.-W. Kim and Kang wrote the manuscript, which was critically revised by all of the authors. All of the authors approved the final version submitted for publication.